The goal of this application is to support the development of Dr. Peter M. Snyder as a clinician scientist so that at the completion of the award he will be an independent researcher and an outstanding academic scientist and clinician. Dr. Michael J. Welsh will assume responsibility as mentor to ensure the success of the development plan. The heart of the proposal is an intensive training experience in the basic research laboratory. Dr. Snyder will study the epithelial Na+ channel, ENAC. Mutations in the Beta and gammaENaC subunits of ENaC cause Liddle's syndrome, an inherited form of hypertension. Dr. Snyder's preliminary studies indicate that Liddle's mutations increase Na+ current through ENaC. The three major aims of his research proposal are to understand how Liddle's-associated mutations increase ENaC Na+ current, how ENaC is regulated, and how the ENaC subunits contribute to the formation of a Na+ channel pore. These basic studies will provide him with training required to develop skills in molecular biology, cell biology, and patch-clamp electrophysiology. In addition, he will further develop his skills at using the scientific method to develop hypotheses that can be experimentally tested to yield unequivocal answers. In addition to basic research training Dr. Snyder will continue his training in biologic science with didactic courses, seminars and journal clubs. He will receive instruction in speaking and writing and will receive instruction in the responsible conduct of research. He will also attend national meetings to present his own work and to learn from others. Both the mentor and the institution are highly committed to the applicant's scientific development and academic success.